The band's name comes from a term coined by detective novelistDashiell Hammett. The term apparently describes the addled, fearful mindset people are in after a prolonged immersion in violent situations. The term was coined in the novel Red Harvest, which is also the title of Bloodsimple's second album.

In May, the band was featured on the soundtrack to the film House of Wax, with their song "Path to Prevail."[7] In its first week of release, A Cruel World sold 3,120 copies, according to Nielsen SoundScan.[8] In April, Bloodsimple were rumored to be the band given the second "mystery band" slot on the second stage at Ozzfest.[9] However, that report was later refuted by a spokesperson for Ozzfest.[10]

In June 2005, Bloodsimple began touring the U.S. with American Head Charge and Static-X.[11] Also in June, drummer Brendon Cohen joined bassist Mike Fleischmann, vocalist B. Folly and guitarist Skullion to form a new band named Karnov.[12] Bloodsimple then teamed up with Byzantine, Gizmachi and headliners Six Feet Under for the "Masters of Brutality" U.S. tour that was to begin in July.[13] However, the tour was postponed. On July 26, the music video for "What If I Lost It," off the band's debut album, was posted on MySpace.[14] On August 27, it was announced that the band, along with Disturbed, Dope, and Life of Agony, among others where scheduled to appear at Locobazooka! in September.[15] On August 31, it was announced that the band's song "Overload" would appear on the Master's of Horror soundtrack.[16]

On September 11, the tracklisting for Roadrunner Records' Roadrunner United compilation album was revealed, and it showed that Bloodsimple vocalist Tim Williams would be performing on the track "Army of the Sun."[17] Then five days later, it was announced that the band's song "September" would be featured on the Saw II soundtrack.[18] On September 24, 2005, the band's concert at Club Voltage in Levittown, New York included an unannounced reunion performance by Vision Of Disorder vocalist Tim Williams and guitarist Mike Kennedy.[19] Throughout October and November the band performed with Throwdown, Soulfly and Incite.[20] On December 5, it was announced that the band's song "Sell Me Out" would be appearing on the Best of The Taste of Chaos compilation two-CD set.[21] On December 19, Roadrunner Records posted a list of some of their artists' selections for the top 10 albums of the year, and both Brock Lindow of 36 Crazyfists and Chris Spicuzza of Chimaira selected Bloodsimple's A Cruel World as the seventh best album of 2005.[22]

Bloodsimple began 2006, by performing in support of Disturbed on the Jägermeister Music Tour.[23] In March, the band was scheduled for "The Crusade III: Ascend Above the Ashes" tour in the U.K. and Ireland along with God Forbid and Trivium.[24] In May, drummer Chris Hamilton left Bloodsimple, forming a new band named Saint Caine along with former Dropbox members vocalist / guitarist John Kosco and guitarist Joey Wilkinson and bassist John Eville.[25] Drummer Brendon Cohen toured as a replacement for the summer of 2006, resulting in three fifth's (75%) of Vision Of Disorder's old lineup playing a limited number of shows.

Bloodsimple performed at the Loud Park 06 festival on October 14 and 15 at the Makuhari Messe International Exhibition Halls in Tokyo, Japan.[32] In December, the band posted a cover of The Doors' "Five to One" on their MySpace page.[33]

Bloodsimple were reported to begin a tour with Diecast and Sevendust on February 8, 2007 in Fort Wayne, Indiana.[34] However, on December 20, it was that report was refuted by Bloodsimple saying; "We're putting the finishing touches on the record this week and will mix it first thing in January 2007, then wait on official release date and touring plans which will hopefully be in March."[35]

On April 21, it was announced that Bloodsimple, along with Medication, would be an opening act for Hellyeah in May.[36] On May 28, it was announced that the band's next album was originally scheduled to be released in July.[37] However, the album's release was postponed.

Bloodsimple then spent the latter part of May and most of June touring in Europe, performing at festivals and clubs.[38] Some of the performances that month include; performimg on the "Dimebag Darrell Stage" at the Download Festival in Donington Park, Leicestershire.,[39] performing at the Fields of Rock festival in Biddinghuizen, the Netherlands on June 16,[40] performing at the Bilbao DDK Live Festival 2007, in Bilbao, Euskal Herria, Spain on June 21,[41] performing at the Hellfest in Clisson, France on June 22,[42] and performing between June 23–24 in Dessel, Belgium at the Metal Dome as part of the Graspop Metal Metting.[43] Then on July 29, Bloodsimple was added to the Family Values Tour, and would be performing on the second-stage.[44] However, on September 1, the band issued a statement announcing that they were forced to cancel their appearances on the final three days of the Family Values tour, due to vocalist Tim Williams having a tooth pulled.[45]

On October 30, the same day as their new album's release, the band began touring in support of Hellyeah on the "Balls Volume Strength" tour.[46] That same day, the band's long delayed second album, Red Harvest was released in the U.S. through Bullygoat/Reprise Records. It was produced by Machine, who had produced records for many successful acts such as Eighteen Visions and Lamb of God. In its first week of release, the album sold 2,400 copies.[47] On November 20, Bloodsimple was scheduled to perform in Amarillo, Texas along with Hellyeah and Otep, however, on the day of the concert, it was announced that that nights concert had been cancelled.[48]

Bloodsimple then opened for Avenged Sevenfold from January 17 through February 1.[49] Then, that same month, the music video for the band's next single "Out to Get You" began streaming on the official website for Metal Hammer. The video features footage from the movie Night of the Living Dead by George A. Romero.[50] In April, the band joined Korn, Biohazard, and Chimaira on a six show tour of Australia and New Zealand.[51] Then on April 9, it was announced that they had been nominated for an award at the 2008 "Metal Hammer Golden Gods" awards. They were nominated, along with Still Remains, Apocalyptica, DevilDriver, and Every Time I Die, for "Breakthrough Artist."[52] Bloodsimple were then schdeuled to appear on WSOU's 60th Anniversary show on April 18, however, just six days prior to the show, it was announced that they had been replaced by Anaka.[53] On April 16, it was announced that Bloodsimple was scheduled to perform at Rockfest, in Kansas City, Missouri.[54] However on May 30 bassist Kyle Sanders issued a statement stating:

Due to circumstances out of our control, Bloodsimple is NOT on Rockfest in Kansas City June 7th, and we are not on tour with Sevendust. We apologize to all fans who planned on hanging out with us and we are deeply sorry to all in the Sevendust camp, but we were forced to drop off the tour due to a loss in the band's family. We're all extremely disheartened about this and hope to be back in the saddle soon.